Melatonin promotes distal dendritic ramifications in layer II/III cortical pyramidal cells of rats exposed to toluene vapors

We have previously shown that toluene inhalation produces significant impairments in the basilar dendritic outgrowth of pyramidal cortical cells. This neurotoxic effect was markedly inhibited by melatonin administration at a dose of 5 mg kg− 1. The present study was designed to determine whether toluene and melatonin equally affect all basilar dendritic segments or if a differential response exists between the segments. Twenty-eight male mice were weaned at postnatal day 21 (P21) and randomly assigned to either the control (C; n = 10,) or toluene (T; n = 18) group. Between P22-P32, male rats were placed into a glass chamber and exposed to either toluene vapors (5–000–6000 ppm) or clean air for 10 min a day. When toluene exposure ended (P32), animals were further assigned to the following experimental groups: (a) control/saline (C/S; n = 10), (b) toluene/saline (T/S; n = 10), or (c) toluene/melatonin 5 mg kg− 1 (T/M; n = 8). Melatonin or vehicle solutions were administered daily between P32 and P38. Forty-eight hours after the final toluene exposure, the animals were sacrificed, and the pyramidal cortical cells were stained using the Golgi–Cox–Sholl procedure. The number of basilar dendritic branches/order was counted using the centrifugal ordering method. The results indicate that (i) toluene inhalation significantly impairs both proximal and distal basilar dendritic ramifications (in the parietal and frontal/occipital cortices, respectively) and (ii) melatonin both protects neurons from toluene neurotoxicity in all cortical areas studied and increases the complexity of the dendritic tree above control values.

Research Highlights
► Toluene inhalation differentially impairs the basilar dendritic morphology of neocortical pyramidal cells (parietal cells are more affected than proximal ones, whereas distal branches are more impaired in frontal and occipital pyramidal cells).
► The neuronal impairment detected in toluene-exposed animals was significantly recovered by melatonin administration.
► Melatonin exerts a trophic-like effect, mainly in the distal branches of frontal and parietal cells.